Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications. No specific antidotes are available for organochlorine poisoning; rather, the medications used in these cases include gastrointestinal decontaminants, beta-blockers, vasopressors, and benzodiazepines and other anticonvulsants.

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Antidotes

Class Summary

These agents adsorb GI toxins, which are then fecally excreted, thus minimizing systemic absorption. They may not adsorb hydrocarbons and other toxins. They are beneficial only if administered within 1-2 h of ingestion.

Besides adsorbing toxins, activated charcoal creates a diffusion gradient in the GI circulation (ie, a "sink" effect), which draws the absorbed drug into the GI tract for binding and elimination. Administer after careful risk-to-benefit consideration, and most likely after consultation with a poison control center or a medical toxicologist.

Activated charcoal is an emergency treatment for poisoning caused by drugs and chemicals. The network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. It does not dissolve in water.

For maximum effect, administer within 30 minutes of ingesting poison. Multiple-dose activated charcoal (MDAC) may be administered at 10-20 g q2-4h without a cathartic.

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Bile acid sequestrants

Class Summary

These binding agents are used in the treatment of hypercholesterolemia and have been noted to bind certain lipid-soluble substances, as well as substances that are normally recirculated through the biliary-enterohepatic and enteroenteric system.

Cholestyramine is a nonabsorbable bile acid–binding anion exchange resin that forms a nonabsorbable complex with bile acids in the intestine, which in turn inhibits enterohepatic reuptake of intestinal bile salts.

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Beta-Blockers

Class Summary

Ventricular dysrhythmias may respond to beta-adrenergic blockade therapy. In contrast, if mixed adrenergic stimulation is highly suspected acutely, do not use beta-blockers because of the possibility of developing deleterious unopposed alpha-adrenergic stimulation.

This category of drugs has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In the setting of myocardial ischemia, beta-blockers have antiarrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.

Consider an alpha-agonist, such as phenylephrine, for the treatment of hypotension that does not respond to fluid replacement.

Alpha Adrenergic Agonists

Class Summary

Phenylephrine is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body and increases peripheral venous return. It is useful in treating hypotension. Theoretically, using pure alpha-agonists for hypotension is better because of sensitized myocardium.

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Anxiolytics, Benzodiazepines

Class Summary

A sedative hypnotic with rapid onset of effects and a relatively long half-life, lorazepam is the drug of choice for seizure control in patients with organochlorine-induced seizures. The rate of injection should not exceed 2 mg/min. Lorazepam may be administered intramuscularly if intravenous access cannot be obtained.

By increasing the action of gamma aminobenzoic acid (GABA), a major inhibitory neurotransmitter in the brain, lorazepam may depress CNS function at all levels, including limbic and reticular formation. Monitor the patient's blood pressure after administering a dose of lorazepam and adjust subsequent doses as necessary.

Midazolam is used as alternative agent for termination of refractory status epilepticus. Because it is water soluble, midazolam takes approximately 3 times longer than diazepam to reach peak effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating a procedure or repeating the dose. Midazolam may be administered intramuscularly if vascular access cannot be obtained.

Diazepam depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. If convulsions persist despite treatment with diazepam, administer an alternative anticonvulsant.

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Anticonvulsants, Hydantoins

Class Summary

Phenytoin and fosphenytoin are second-line agents for acute control of seizures. The antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate, so concomitant administration of an IV benzodiazepine will usually be necessary to control seizures.

Phenytoin must be administered slowly and therefore takes longer to enter the brain than benzodiazepines. However, it has the advantage of a long duration of action and can be administered orally after acute illness.

Phenytoin is not water-soluble and must be solubilized in a propylene glycol carrier with a pH of 12 to prepare an IV form. Therefore, it cannot be given more rapidly than 50 mg/min without risk of significant hypotension and cardiac arrhythmias. It also carries the major risk of potential irritation at the IV site and vascular compromise of the infused limb. Therefore, its use in status epilepticus should be avoided if possible.

Fosphenytoin is a diphosphate ester salt of phenytoin that acts as a water-soluble prodrug of phenytoin. After administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.

To avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express the dose as phenytoin sodium equivalents (PE). Although it can be administered IM, the IV route is route of choice and should be used in emergency situations.

This drug carries an FDA Black Box warning cautioning against exceeding a rate of administration of 150 mg PEs per minute, due to risk of severe hypotension and cardiac arrhythmias.

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Anticonvulsants, Barbiturates

Class Summary

These agents have direct effects on the benzodiazepine–GABA-A–chloride receptor complex in enhancing chloride flux.

Pentobarbital is a short-acting barbiturate that interferes with transmission of impulses from the thalamus to the cortex. It has sedative, hypnotic, and anticonvulsant properties. It is a second-line drug for treatment of drug-induced seizures.

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General Anesthetics, Systemic

Class Summary

Propofol, an intravenous anesthetic agent, is active on the glutamate and GABA-A receptors, similar to alcohol itself, whereas benzodiazepines are active only against the GABA receptors. Due to its rapid onset of hypnosis and anticonvulsant properties, propofol is an alternative treatment for patients who are refractory to high-dose benzodiazepines. Advantages to its use are that it is easily titratable, with predictable effects, and has a rapid metabolic clearance.

Propofol is a phenolic compound unrelated to other types of anticonvulsants that has general anesthetic properties when administered IV. Growing numbers of anecdotal reports describe successful use of propofol in refractory status epilepticus. Intubation and ventilation are required. Hypotension may require treatment.

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Beta2 Agonists

Class Summary

Bronchodilators may be used to relieve respiratory distress from organochlorine toxicity. Conceptually, however, beta-agonists could precipitate cardiac dysrhythmias in sensitized myocardium and hence should be used with caution in patients exposed to organochlorines.

Anticholinergics, Respiratory

Class Summary

These agents are competitive inhibitors of acetylcholine and muscarine in the autonomic nervous systems and they relieve muscarinic effects, especially bronchorrhea. Inhaled anticholinergic agents (eg, ipratropium) may be considered. One caveat is that conceptually, anticholinergics can precipitate cardiac dysrhythmias in sensitized myocardium and should be used with caution in patients exposed to organochlorines.